Frontiers in Immunology (Jan 2022)

Co-Expression of miR155 or LSD1 shRNA Increases the Anti-Tumor Functions of CD19 CAR-T Cells

  • Jing Zhang,
  • Jingjing Zhu,
  • Genhui Zheng,
  • Qianyu Wang,
  • Xiaorui Li,
  • Yaru Feng,
  • Fengqin Shang,
  • Siqi He,
  • Qiyao Jiang,
  • Bingjie Shi,
  • Dong Wang,
  • Zhiwei Cao,
  • Jianxun Wang,
  • Jianxun Wang

DOI
https://doi.org/10.3389/fimmu.2021.811364
Journal volume & issue
Vol. 12

Abstract

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Chimeric antigen receptor (CAR) T cells targeting CD19 antigen have produced remarkable clinical outcomes for cancer patients. However, identifying measures to enhance effector function remains one of the most challenging issues in CD19-targeted immunotherapy. Here, we report a novel approach in which a microRNA (miRNA) or short-hairpin RNA (shRNA) cassette was integrated into CAR-expressing retroviral vectors. Using this system, we generated anti-CD19 CAR-T cells co-expressing miR155 or LSD1 shRNA and found that anti-CD19 CAR-T cells with miR155 upregulation or LSD1 downregulation exhibited increased anti-tumor functions in vitro and in vivo. Transcriptional profiling analysis by RNA sequencing revealed the targets of miR155 and LSD1 in anti-CD19 CAR-T cells. Our experiments indicated that introduction of miRNA or shRNA expression into anti-CD19 CAR T-cells might be an effective strategy to improve the anti-tumor effects of CAR-T cell therapy.

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